Effect of Aβ protein on inhibiting proliferation and promoting apoptosis of retinal pigment epithelial cells

AIM: To identify the effect and regulatory mechanism of amyloid beta (A beta) protein on retinal pigment epithelial (RPE) cells in cell proliferation and apoptosis, and clarify A beta role in the pathogenesis of age-related macular degeneration (AMD). METHODS: The model of A beta 25-35 protein cytotoxicity in RPE cell was successfully established to investigate the effect of A beta protein on RPE cells in vitro. Based on A beta protein, the specific inhibitors (HY-50682 or BAY11-7082) or activating agent (lipopolysaccharide) was used to analyze the regulatory mechanism of A beta protein to RPE cells on cell proliferation and apoptosis by flow cytometry, real-time polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay and dual-luciferase reporter gene assay. RESULTS: The number of RPE cells, treated with A beta 25-35 from 0.3 to 60 mu mol/L, significantly reduce (P<0.01), and had the dose-dependent effect. A beta protein 60 mu mol/L inhibits the G1/S phase transition (P<0.01) and down-regulated cyclin E mRNA level (P<0.01). Similarly, A beta 25-35 induced a significant increase of cell apoptosis, accompanied by the significantly higher level of activated caspase 3 protein. Furthermore, nuclear factor-kappaB (NF-kappa B) activity and phosphorylated I kappa-Ba level would significantly lower in treated RPE cells. Using specific inhibitors or activating agent based on the A beta, the cell numbers, NF-kappa B activity, phosphorylated I kappa-Ba level, receptor for advanced glycation endproducts (RAGE) gene expression levels, cyclin E mRNA level and activated caspase 3 level had accordingly changed by different methods, confirming that RAGE/NF-kappa B signaling pathway involved in the regulation of A beta protein on RPE cell apoptosis and proliferation. CONCLUSION: A beta protein inhibits cell proliferation and activates apoptosis via inactivation of the RAGE/NF-kappa B signaling pathway in RPE cell.